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Biomedical subjects

M A Katz

Publications and source records attributed to M A Katz.

At least 19 recordsLinked to original sources
PubMed1995

Albumin reduces basement membrane hydraulic conductance in part due to arginyl side groups.

Albumin reduces capillary hydraulic conductance (Lp) even at low concentrations. To determine if part of this barrier protective effect might be extracellular, we studied the effects of bovine serum albumin (BSA) on Lp of self-assembled basement membrane (Matrigel). Lp with tris(hydroxymethyl)aminomethane (Tris) buffer superfusate was stable at 1.77 +/- 0.22 x 10(-5) (SE) cm.s-1.cmH2O-1 over several hours. At 0.1 g/dl BSA, experimental/control (Tris) Lp fell to 83.1 +/- 6.0% (2P < 0.025), with decreases to 72.4 +/- 3.7% at 1 g/dl (2P < 0.005), 45.3 +/- 5.1% at 2.5 g/dl (2P < 0.001), and 45.0 +/- 4.8% at 4.0 g/dl (2P < 0.001). In separate experiments, BSA arginine groups were neutralized by 1,2-cyclohexanedione (CHD), and experimental/control Lp values were measured. At 2.5 g/dl, CHD-BSA depressed Lp to 54.4 +/- 4.8%, while unmodified BSA reduced Lp to 40.8 +/- 3.5% of Tris control (2P = 0.05). Finally, soluble arginine at three- and sixfold the arginine in BSA was added to BSA superfusate. For threefold, Lp rose to 120 +/- 8% of BSA level and for sixfold to 129 +/- 9% (2P < 0.05). We conclude that some part of the albumin protective effect is very likely due to consequences on extracellular matrix and that at least 18-22% of this effect is related to arginine groups on albumin when computed from Lp, and up to 34% when viscosity is taken into account. Membrane-saturable arginine-binding sites can be unbound with arginine, thus nullifying part of the barrier protective effect of BSA.

Animals↗
PubMed1994

The fate of hypertonic saline administered during hemodialysis.

The possibility of postdialysis hypernatremia is one reason nephrology nurses do not administer hypertonic saline (HS) to treat hypotension or muscle cramps during the last hour of hemodialysis (HD). A single group time series quasi-experimental design was used to evaluate the effect of 50 mEq of HS given during the last hour of HD on interdialytic weight and serum sodium (PNa) and dialysate sodium (DNa) levels. Ten subjects experiencing hypotension or cramps during the last hour of HD, but not during the final 15 minutes, received 50 mEq of HS. One preinjection PNa and DNa sample was obtained, followed by the collection of 8 PNa and 42 DNa samples during the 5 minutes subsequent to the HS injection. Interdialytic weight was evaluated for differences. The results indicated that a statistically significant, but minor amount of sodium was removed in the dialysate (8.77% mEq/L + .96). In addition, the amount of sodium retained over a longer time scale was clinically insignificant, as evidenced by no significant change in the interdialytic weight following administration of 50 mEq of HS. PNa rose 12.7 + 1.3 mEq/L to a peak of 152.2 + 1.6 mEq/l in 54 + 2 seconds, returning to 3 + 0.3 mEq above baseline at 5 minutes. In conclusion, administration of HS up to the final 15 minutes of HD is safe therapy for hypotension and muscle cramps because it does not cause an increased interdialytic weight gain.

Adult↗
PubMed1993

Experimental preeclampsia produced by chronic constriction of the lower aorta: validation with longitudinal blood pressure measurements in conscious rhesus monkeys.

OBJECTIVES: Our goals were (1) to determine whether hypertension, proteinuria, and glomerular endotheliosis can be produced by chronic reduction of lower aortic pressure in pregnant rhesus monkeys and (2) to study the time course of the development of hypertension by means of longitudinal arterial blood pressure measurements in conscious, unrestrained pregnant rhesus monkeys. STUDY DESIGN: Indwelling arterial catheters were placed at 103 +/- 4 days of gestation (term 160 days) for measurement of arterial pressure before and after reduction of lower aortic pressure. At 116 +/- 7 days lower aortic pressure was reduced by 24 +/- 11 mm Hg in 11 monkeys (experimental group) by a stricture on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting on the aorta just below the renal arteries; six monkeys (controls) underwent a sham operation. Resting pressures were measured three to five times per week by a tether-and-swivel system. RESULTS: Baseline arterial pressure averaged 81 +/- 6 mm Hg. In the experimental group four monkeys had adverse outcomes (one maternal death with severe hypertension, one abruptio placentae with stillbirth, and two spontaneous preterm deliveries with hypertension). There was one preterm delivery in the control group. Of the seven monkeys with aortic stricture who continued to term, four developed sustained hypertension (mean pressure 18 +/- 6 mm Hg above baseline), proteinuria, and moderate-to-severe glomerular endotheliosis. None of the controls had hypertension or proteinuria, but two had endotheliosis. CONCLUSION: These observations confirm that a syndrome resembling preeclampsia can be produced by a reduction of lower aortic pressure, and they demonstrate that the associated hypertension is not an artifact of anesthesia. This model may prove useful in studying the pathophysiologic mechanisms of preeclampsia.

Animals↗
PubMed1993

Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys.

OBJECTIVE: Our purpose was to investigate whether a reduction in uteroplacental perfusion pressure would produce changes in trophoblast-uterine interactions at the cellular level. STUDY DESIGN: Strictures were placed around the abdominal aortas of rhesus monkeys at 116 +/- 7 days of pregnancy to reduce uteroplacental perfusion pressure. Placental bed biopsy specimens were obtained at cesarean section, and cytotrophoblasts were identified by means of an anticytokeratin antibody. RESULTS: In monkeys without aortic strictures, interstitial trophoblast invasion was restricted to the outer half of the endometrium. Endovascular trophoblast invasion involved the entire endometrial portion of uterine vessels and extended through the subjacent half of their myometrial segments. In seven of nine monkeys with aortic strictures the depth of interstitial trophoblast invasion was substantially increased and extended throughout the entire decidua and at least a portion of the myometrium. In contrast, the pattern of endovascular trophoblast invasion was identical to that observed in the placental beds of control animals. CONCLUSION: These results suggest that uteroplacental perfusion pressure or oxygen content may be important physiologic factors controlling the depth of interstitial cytotrophoblast invasion.

Animals↗
PubMed1992

Structural change in fiber matrix allows for enhanced permeability and reduced hydraulic conductivity.

Because various diseases, notably diabetes mellitus, are associated with a progressive dissociation within the same organ between hydraulic conductivity (which decreases) and macromolecular permeability (which increases), it was the aim of this study to investigate whether the fiber matrix model for capillary basement membrane and intercellular material can accommodate such clinical findings. Using initial values obtained in this laboratory for a normal fiber radius of .752 nm, a void volume ratio of .627, and a macromolecular test probe radius of 3.6 nm, we found that a wide range of increases in fiber radius and reductions in void volume ratio brought about by fiber dilution are compatible with the clinical observations.

Animals↗
PubMed1992

Hydraulic conductivity of basement membrane with computed values for fiber radius and void volume ratio.

The basement membrane contributes to resistance to ultrafiltration of the capillary wall, but efforts to conduct studies of this material have been hindered by difficulty in obtaining homogenous sources and by compression from high filtration pressures. We utilized Matrigel in a conductivity chamber and showed that it reproducibly yielded a specific hydraulic conductivity of (2.247 +/- 0.328) x 10(-14) cm2, which is within 21% of that obtained for porcine glomerular basement membrane by Robinson and Walton (Microvasc. Res. 38: 36-48, 1989). No compression or hysteresis was observed over 5-25 cmH2O pressure difference. Depending on whether data were fit to drag or hydraulic radius fibermatrix models, fiber radius was 0.626-0.696 nm, and void volume ratio varied between 0.826 and 0.846, the former agreeing with the major components of Matrigel. Ready availability of Matrigel, its uniform hydraulic conductivity, and its fit to fibermatrix theory make it ideal to study changes in basement membrane during physiological and pathological changes. Moreover, results of such studies are likely applicable to endothelial barriers, whose luminal and intercellular surfaces are lined with fibrillar materials.

Basement Membrane↗
PubMed1992

Macromolecular transport across endothelial monolayers.

We studied the macromolecular size-selective transport characteristics of polycarbonate (PC) filters with defined pore radius (rp; 15,000 to 400 A) as well as 2,000 A rp PC filter-bovine pulmonary artery endothelial cell (EC) monolayer sandwich under zero hydrostatic pressure conditions using fluorescein isothiocyanate-hydroxyethyl starch (FITC-HES, 16 A less than ae less than 100 A), and 2-methoxy-2,4-diphenyl-3(2H) furanone-bovine serum albumin (MDPF-BSA, ae = 35.5 A). We surprised to find substantial convective solute transport (solute drag) across the filter-endothelial sandwich. This effect was increased by large rp (15,000 A) filters and prevented by 400 A rp filters. Positive hydrostatic pressure across 2,000 A rp filters increased convective solute transport and negative pressure prevented this effect. High, medium and low permeability monolayers on 2,000 A filters progressively attenuated the solute drag effect seen across these filters without cells. The decline in monolayer permeability was associated with an increased filter area covered by cells; approximately 50 and 95% as well as greater than 99%, respectively. Although significant restricted diffusion was seen across low permeability monolayers, this pattern was distinct from that measured in single frog capillaries. Restricted diffusion by low permeability monolayers under conditions that produce solute drag document the significant barrier effects of high confluence endothelial monolayers, in vitro. These data show that solute transport across endothelial monolayers is due to diffusion+convective solute drag. The degree of the solute drag effect across the filter-endothelial sandwich is a direct function of monolayer confluence.

Animals↗
PubMed1991

Influence of volume expansion on capillary transport in the gut of Pichindé virus infected strain 13 guinea pigs.

Hydropenic strain 13 guinea pigs (GP13) injected with Pichindé virus show marked jejunal capillary disruption determined by a reduction in protein reflection coefficient (sigma) [Katz and Starr, 1990]. These studies examined whether this is reversed by a 2% Ringer's expansion, and whether anorexia may contribute to reduced sigma. GP13 were either infected or given a 60% expected ad lib diet, and were studied while under a 2% Ringer's expansion. The results showed 1) infected GP13 separated into groups with either a persistently low sigma (volume unresponsive) or a normal sigma (volume responsive), but no obvious feature of the animals could predict responsiveness; 2) caloric restriction had minimal to no effect on sigma; and 3) both responsive and unresponsive GP had increased heart, lung, and kidney weights. Volume expansion may have salutary effects in some infected GP13, and this is probably due to pressure mediated effects on the capillary wall. The findings support the possibility that conservative management of hemorrhagic fevers may directly ameliorate capillary leak.

Animals↗
PubMed1991

Convection of macromolecules is the dominant mode of transport across horizontal 0.4- and 3-microns filters in diffusion chambers: significance for biologic monolayer permeability assessment.

The purpose of the present study was to evaluate the permeability characteristics of fluorescein-labeled hydroxyethyl starch (FITC-HES, 20 less than molecular radius, aE less than 111 A) across large pore (0.4- and 3-microns polycarbonate) filters used in endothelial cell monolayer diffusion studies. Although the apparent permeability (P) of the FITC-HES macromolecules across these filters declined as the molecular radius increased, this decline was less than that associated with each solute's free diffusion (D0). Thus, the P/D0 anomalously increased as aE increased, a pattern not seen for free diffusion (flat P/D0 with increased aE) or restricted diffusion (decline in P/D0 with increased aE). Substantial natural convection across the porous filters produced the anomalous P/D0 curve for the following reasons: (1) this effect was elevated with positive pressure and ameliorated by zero driving pressure, and (2) the effect was much greater across filters with large (3 microns) vs small (0.4 microns) pore sizes. In addition, we estimated that less than half of macromolecular transport above 50 A probe radius at zero transmural pressure arrives by diffusion. The findings suggest that the property of restricted diffusion of biologic layers on these filters will be artifactually exaggerated when the measured resistance of the filter is subtracted from that of the filter plus biologic monolayer. Remedies for this problem may include using smaller pore filters, filters layered with extracellular material, or structural methods to determine true filter permeability.

Cell Membrane Permeability↗
PubMed1990

Pichinde virus infection in strain 13 guniea pigs reduces intestinal protein reflection coefficient with compensation.

Pichinde virus inoculation into strain 13 guinea pigs is a model with features reputed to be similar to hemorrhagic fever in humans. Although the infection is lethal by day 13-19, guinea pigs of approximately 600 g do not show edema or effusions. This raises the questions of whether capillary damage is present in such infected animals and, if it is, why edema is absent. The effects of Pichinide virus on protein transport across jejunal capillaries were examined in 38 normal and 7 infected strain 13 guinea pigs 12 days after inoculation. The latter lost 20.3% body weight but maintained normal blood pressure, serum protein concentration, and jejunal lymph flow. However, their protein solvent drag reflection coefficient (sigma) was reduced to .52 +/- .03 (mean +/- SE) from .73 +/- .02 (2P less than .001), while permeability-surface area product was not changed. In the absence of gross edema or effusions, Pichinde virus-infected guinea pigs demonstrated a leaky gut capillary wall to protein compatible with an increase in pore size or large pore number less than sufficient to change permeability-surface area product. Compensatory mechanisms that prevent edema at this stage are efficient and may include reduced capillary pressure or some degree of capillary flow stasis.

Animals↗
PubMed1989

Iron status in patients receiving erythropoietin for dialysis-associated anemia.

Adequate body iron stores are crucial to assuring rapid and complete response to recombinant human erythropoietin (rHuEPO). In the present study, markers of iron storage were examined in 27 patients with normochromic, normocytic anemia undergoing acute rHuEPO (150 to 300 U/kg t.i.w.) treatment for anemia. We calculated projected iron needed for new hemoglobin synthesis from the difference between initial and target hemoglobin concentrations, initial iron reserves available from initial serum ferritin levels, and net projected surplus or deficit from the difference between needs and reserves. Of 22 patients predicted to develop iron deficiency (mean projected deficit 268 +/- 70 mg), 20 developed evidence of exhausted iron stores (transferrin %sat less than 16 or ferritin less than 30 micrograms/liter) before reaching target hemoglobin; two predicted to become deficient (projected deficit less than 100 mg) did not; and all five predicted to avoid iron deficiency (mean projected surplus 177 +/- 20 mg) remained iron replete. During acute rHuEPO therapy net body iron balance remained neutral in patients receiving no iron supplements and increased 5 mg/kg in patients prescribed oral ferrous sulfate. However, in patients given iron dextran i.v. less than 60% of elemental iron administered became measurable as iron stores or usable for hemoglobin synthesis.

Anemia↗
PubMed1989

Ethane production rates and minute ventilation.

Ethane quantitated in the expired alveolar gas is a noninvasive measure of free radical activity. This method has been criticized for lack of control of minute ventilation (VE) in spontaneously breathing animals, although ethane, which is poorly soluble in tissues, should not be affected by changes in VE. We measured ethane elimination rates in six strain 13 guinea pigs (GP13) during spontaneous room air breathing and in six room air breathing, pentobarbital-anesthetized, tracheostomized, externally warmed, mechanically ventilated GP13s at various levels of VE. In the ventilated animals, weight0.75/VE (metabolic activity corrected for VE) was a linear function of arterial CO2 tension (PaCO2) drawn from arterial line (r = 0.72, P less than 0.005). However, weight0.75/VE did not correlate with ethane elimination rates (r = 0.12, not significant). The mean (+/- SD) ethane elimination rates in the spontaneously breathing animals was 3.15 +/- 0.96 pmol.min-1.100 g-1 and was not significantly different from the mean rate in the mechanically ventilated animals (3.11 +/- 1.37) over a range of VE's. These data demonstrate that ethane elimination rates are not affected by changes in VE and are unaffected by pentobarbital anesthesia.

Animals↗
PubMed1989

Source of ethane in expirate of rats ventilated with 100% oxygen.

Ethane in alveolar expirate may have its source in organs other than the lung and be transported to the lung for elimination. We determined ethane production rates in rats (group I) ventilated with hydrocarbon-free air (HFA) before and after exsanguination. To determine whether the lung is the source of increased ethane production during exposure to 100% O2, we measured ethane in the expirate of nine exsanguinated, Sprague-Dawley rats (group II) mechanically ventilated with HFA and then with 100% O2. In all nine animals, ethane elimination rates on 100% O2 increased compared with HFA values. In five of the nine rats, HFA ventilation was reinstated after O2 (group III). In all five, ethane elimination fell with HFA ventilation compared with the value on 100%. Six rats with circulation intact were ventilated with HFA and then 100% O2 (group IV). Ethane production rate for group IV animals breathing HFA was not significantly different from the exsanguinated animals in group II while ventilated with HFA. The mean increase in ethane production for the group II animals was not significantly different from the group IV animals. Lung slices from four other rats (group V) were incubated in saline at 37 degrees C with FeCl2 (10 mg) added to enhance free radical formation. Paired lung samples from the same rat were incubated with either HFA or 100% O2. Headspace gas was analyzed chromatographically for ethane at 120 min. Mean ethane in the O2 samples was higher than for HFA. Rat lung tissue is the main source of increased ethane production during 100% O2 exposure.

Animals↗
PubMed1989

Relationships between microvascular function and capillary structure in diabetic and nondiabetic human skin.

Despite the commonly held view that abnormalities in capillary morphology, in particular thickening of the capillary basement membrane, are partly responsible for diabetic ischemia, few studies have correlated anatomic and hemodynamic variables in the same diabetic subjects. In a previous study of 24 type II (non-insulin-dependent) diabetic subjects and 24 age-matched control subjects, we showed that a standard finger exercise vasodilated cutaneous forearm vessels nearly equally (51%), but the postarteriolar flow responded differently between groups. Nondiabetic subjects increased flow by recruitment of capillaries, whereas diabetic subjects did so by capillary flow augmentation. Moreover, resting permeability-surface area product (PS) to pentetic acid was 85% higher in diabetic than nondiabetic subjects. In this study, these same subjects had their forearm skin biopsied and examined morphometrically by electron microscopy for capillary radius, basement membrane thickness, endothelial cell density, and a folding index of luminal membrane reduplication. All morphological variables were correlated stepwise in a saturated, analysis of covariance model with the physiological results. The correlations were sparse and specifically excluded basement membrane thickness. The highest r2 value was .432 between resting PS and a ratio of capillary density to endothelial cell number per capillary. These studies show little evidence that diabetic microvascular physiological variables are tightly connected to morphometric changes except for minor permeability changes, which rise with capillary density and decrease with endothelial cell number. Because PS to pentetic acid is increased in diabetic subjects at any level of capillary density, it seems reasonable that permeability may be increased above that of nondiabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillaries↗
PubMed1988

Ethane production rate in rats exposed to high oxygen concentration.

Production rates for ethane gas, a hydrocarbon byproduct of lipid peroxidation, measured from the ethane present in the exhaled breath of rats, were used to determine changes in oxygen-free radical activity. Rates of ethane production were measured in rats housed in metabolic chambers and exposed to room air and to high oxygen concentrations. Expired ethane, adsorbed onto activated charcoal and then liberated by heating, was measured by gas chromatography. Ethane production rates in groups of 8 rats increased during 8 h of 100% oxygen exposure from a mean (+/- SE) room air value of 11.30 +/- 1.15 to 27.85 +/- 2.93 pmol/min/100 g rat (p less than 0.005). The mean (+/- SE) percent increases in ethane production after exposure to 100% oxygen in 8 rats pretreated with 0.1 mg/100 g of vitamin E in corn oil vehicle (0.1 ml/100 g) injected intraperitoneally and in a group of 5 rats injected with vehicle alone averaged 157.16 +/- 37.83% and 150.98 +/- 25.19%, respectively. The percent changes noted were not significantly different as measured by analysis of variance. These data indicate that lipid peroxidative activity, hence oxygen-free radical activity, increases in normally fed rats exposed to hyperoxia at a time prior to the previously reported neutrophil influx into the lungs of similarly exposed rats and that it is not attenuated by pretreatment with vitamin E.

Analysis of Variance↗
PubMed1987

Defective vasodilation response to exercise in cutaneous precapillary vessels in diabetic humans.

Although anatomic abnormalities in capillary structure are well described in diabetes mellitus, physiologic responses of diabetic microcirculation are less clear. This study addresses whether cutaneous vasodilation occurs normally in diabetic subjects in response to a standard exercise of underlying muscle. The methods involve a washout analysis from forearm skin of the fast-moving isotope 133Xe and the diffusion-limited marker 111In-diethylenetriamine pentaacetic acid. Twenty-four normotensive type II diabetic patients of age (mean +/- SE) 59 +/- 1.4 yr were age and weight matched with 24 controls. Control subjects increased flow 50.6 +/- 6.4%, which was not different from the increase in diabetic subjects of 52.7 +/- 7.6%. Permeability-surface-area product (PS) increased in control subjects from 1.77 +/- 0.20 ml.min-1.100 g-1 to 3.79 +/- 0.50 (2P = .0001), whereas diabetic subjects did not show a change in PS (3.29 +/- 0.35 to 2.69 +/- 0.31). Resting PS was higher in diabetic than control subjects (P = .0003), perhaps indicating an already recruited capillary bed. During repetitive exercise, control subjects increased capillary density 125 +/- 27% (2P = .0001) above basal with a nonsignificant 14 +/- 8.4% decrease in mean capillary blood flow. Diabetic subjects responded with a nonsignificant decrease in capillary density and a significant 139 +/- 38% increase in capillary blood flow (2P = .001). It is concluded that, although overall vasodilation occurs normally in diabetic cutaneous circulation, the mechanism is different from the normal response in that flow increases by augmentation of capillary flow rather than by recruitment. This is consistent with the thesis promulgated by others that diabetic precapillary vessels have depressed vasodilatory responses or are already maximally vasodilated. The ability of diabetic subjects to vasodilate by augmentation was not correlated with years of diabetes or use of insulin and only slightly negatively correlated with random blood glucose levels (r = -.423, P less than .05).

Aged↗